Cargando…

Targeting Internalized Staphylococcus aureus Using Vancomycin-Loaded Nanoparticles to Treat Recurrent Bloodstream Infections

The bacterial pathogen Staphylococcus aureus is a leading cause of bloodstream infections, where patients often suffer from relapse despite antibiotic therapy. Traditional anti-staphylococcal drugs display reduced effectivity against internalised bacteria, but nanoparticles conjugated with antibioti...

Descripción completa

Detalles Bibliográficos
Autores principales: Nader, Danielle, Yousef, Fajer, Kavanagh, Nicola, Ryan, Benedict K., Kerrigan, Steven W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156000/
https://www.ncbi.nlm.nih.gov/pubmed/34068975
http://dx.doi.org/10.3390/antibiotics10050581
_version_ 1783699335325679616
author Nader, Danielle
Yousef, Fajer
Kavanagh, Nicola
Ryan, Benedict K.
Kerrigan, Steven W.
author_facet Nader, Danielle
Yousef, Fajer
Kavanagh, Nicola
Ryan, Benedict K.
Kerrigan, Steven W.
author_sort Nader, Danielle
collection PubMed
description The bacterial pathogen Staphylococcus aureus is a leading cause of bloodstream infections, where patients often suffer from relapse despite antibiotic therapy. Traditional anti-staphylococcal drugs display reduced effectivity against internalised bacteria, but nanoparticles conjugated with antibiotics can overcome these challenges. In the present study, we aimed to characterise the internalisation and re-emergence of S. aureus from human endothelial cells and construct a new formulation of nanoparticles that target intracellular bacteria. Using an in vitro infection model, we demonstrated that S. aureus invades and persists within endothelial cells, mediated through bacterial extracellular surface adhesion, Fibronectin-binding protein A/B. After internalising, S. aureus localises to vacuoles as determined by transmission electron microscopy. Viable S. aureus emerges from endothelial cells after 48 h, supporting the notion that intracellular persistence contributes to infection relapses during bloodstream infections. Poly lactic-co-glycolic acid nanoparticles were formulated using a water-in-oil double emulsion method, which loaded 10% vancomycin HCl with 82.85% ± 12 encapsulation efficiency. These non-toxic nanoparticles were successfully taken up by cells and demonstrated a biphasic controlled release of 91 ± 4% vancomycin. They significantly reduced S. aureus intracellular growth within infected endothelial cells, which suggests future potential applications for targeting internalised bacteria and reducing mortality associated with bacteraemia.
format Online
Article
Text
id pubmed-8156000
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-81560002021-05-28 Targeting Internalized Staphylococcus aureus Using Vancomycin-Loaded Nanoparticles to Treat Recurrent Bloodstream Infections Nader, Danielle Yousef, Fajer Kavanagh, Nicola Ryan, Benedict K. Kerrigan, Steven W. Antibiotics (Basel) Article The bacterial pathogen Staphylococcus aureus is a leading cause of bloodstream infections, where patients often suffer from relapse despite antibiotic therapy. Traditional anti-staphylococcal drugs display reduced effectivity against internalised bacteria, but nanoparticles conjugated with antibiotics can overcome these challenges. In the present study, we aimed to characterise the internalisation and re-emergence of S. aureus from human endothelial cells and construct a new formulation of nanoparticles that target intracellular bacteria. Using an in vitro infection model, we demonstrated that S. aureus invades and persists within endothelial cells, mediated through bacterial extracellular surface adhesion, Fibronectin-binding protein A/B. After internalising, S. aureus localises to vacuoles as determined by transmission electron microscopy. Viable S. aureus emerges from endothelial cells after 48 h, supporting the notion that intracellular persistence contributes to infection relapses during bloodstream infections. Poly lactic-co-glycolic acid nanoparticles were formulated using a water-in-oil double emulsion method, which loaded 10% vancomycin HCl with 82.85% ± 12 encapsulation efficiency. These non-toxic nanoparticles were successfully taken up by cells and demonstrated a biphasic controlled release of 91 ± 4% vancomycin. They significantly reduced S. aureus intracellular growth within infected endothelial cells, which suggests future potential applications for targeting internalised bacteria and reducing mortality associated with bacteraemia. MDPI 2021-05-14 /pmc/articles/PMC8156000/ /pubmed/34068975 http://dx.doi.org/10.3390/antibiotics10050581 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nader, Danielle
Yousef, Fajer
Kavanagh, Nicola
Ryan, Benedict K.
Kerrigan, Steven W.
Targeting Internalized Staphylococcus aureus Using Vancomycin-Loaded Nanoparticles to Treat Recurrent Bloodstream Infections
title Targeting Internalized Staphylococcus aureus Using Vancomycin-Loaded Nanoparticles to Treat Recurrent Bloodstream Infections
title_full Targeting Internalized Staphylococcus aureus Using Vancomycin-Loaded Nanoparticles to Treat Recurrent Bloodstream Infections
title_fullStr Targeting Internalized Staphylococcus aureus Using Vancomycin-Loaded Nanoparticles to Treat Recurrent Bloodstream Infections
title_full_unstemmed Targeting Internalized Staphylococcus aureus Using Vancomycin-Loaded Nanoparticles to Treat Recurrent Bloodstream Infections
title_short Targeting Internalized Staphylococcus aureus Using Vancomycin-Loaded Nanoparticles to Treat Recurrent Bloodstream Infections
title_sort targeting internalized staphylococcus aureus using vancomycin-loaded nanoparticles to treat recurrent bloodstream infections
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156000/
https://www.ncbi.nlm.nih.gov/pubmed/34068975
http://dx.doi.org/10.3390/antibiotics10050581
work_keys_str_mv AT naderdanielle targetinginternalizedstaphylococcusaureususingvancomycinloadednanoparticlestotreatrecurrentbloodstreaminfections
AT youseffajer targetinginternalizedstaphylococcusaureususingvancomycinloadednanoparticlestotreatrecurrentbloodstreaminfections
AT kavanaghnicola targetinginternalizedstaphylococcusaureususingvancomycinloadednanoparticlestotreatrecurrentbloodstreaminfections
AT ryanbenedictk targetinginternalizedstaphylococcusaureususingvancomycinloadednanoparticlestotreatrecurrentbloodstreaminfections
AT kerriganstevenw targetinginternalizedstaphylococcusaureususingvancomycinloadednanoparticlestotreatrecurrentbloodstreaminfections